Allergy and parasites

Question 1

What is a hypersensitivity reaction?

Answer 1

A persistent immune response in the absence of a true pathogen, causing inappropriate response that is detrimental to host. Usually in response to innocuous allergens.

Question 2

What is a type I sensitivity reaction?

Answer 2

IgE mediated mast cell degranulation and eosinophil activation = Allergy IgE response
Usually against food, drug, venom, hayfever, anaphlaxis

Question 3

What is a type II sensitivity reaction?

Answer 3

IgG autoantibody damaging self cells = AI / cytotoxic IgG

Causes AI haemolytic anaemia, myasthenia gravis, Goodpasture’s, idiopathic thrombocytopenia purpura.

Question 4

What is a type III sensitivity reaction?

Answer 4

IgG - antigen immune complex damage = immune complex disease

Causes serum sickness, arthus reaction, SLE, cryoglobulinaemia.

Question 5

What is a type IV sensitivity reaction?

Answer 5

T cell mediated cellular response = Delayed hypersensitivity.
Causes contact dermatitis, delayed drug reaction, mantoux test

Question 6

What is the difference between type I and IV?

Answer 6

Type I is immediated, within minutes, and life threatening. The cause is easily identified.
Type IV occurs >4hrs after antigen exposure due to T cell migration.

Question 7

What tests are used to identify allergen of type I reaction?

Answer 7

IgE skin prick - allergen pricked into skin. Causes reaction within 10 minutes as the mast cells lie underneath the skin. Only shows sensitisation so requires Pt clinical and temporal Hx to confirm.
Serum testing.

Question 8

What test can be used to identify the allergen of a type IV reaction?

Answer 8

Patch testing - On removal of the patch, if the rash fades it is an irritant but if the rash continues to get worse over 5 days it is an allergen inducing IV.

Question 9

What other types of reactions may occur that are not allergies?

Answer 9

Irritant response to a burn or chemical.
Food intolerance
Side effect to a drug

Question 10

Why is it possible to develop allergies throughout life?

Answer 10

Allergies only develop on 2nd exposure, once the immune system has been sensitised to the allergen.

Question 11

What induces Ig class switching in type I reaction?

Answer 11

Th2 cells produce IL-4 and IL-13 to trigger IgE switching.

Question 12

What inhibits class switching?

Answer 12

Production of IFNgamma by Th1 cells

Question 13

Why does class switching sensitise the Pt to an allergen?

Answer 13

Class switching produces long term memory so on re-exposure the allergen induces the IgE mediated response.

Question 14

Define atopic.

Answer 14

The genetic tendency to develop allergic disease due to predisposition e.g. polymorphism in IL-4 R or FCeR1. At increased risk of asthma, dermatitis, rhinitis and multiple allergies.

Question 15

What is the hygiene hypothesis?

Answer 15

Exposure to bacteria and viruses in early life reduces the risk of developing an allergy by skewing the immune system towards Th1 response.

Question 16

Describe the stages involved in an IgE mediated response?

Answer 16

1) A specific IgE recognises an allergen
2) The extra constant region of IgE bind with high affinity to the IgE-allergen complex to effector cells via FCeR1.
3) Mainly binds to mast cells in tissue and basophils in the circulation.
4) The cross linking causes degranulation.
5) Induces the acute phase response upon release of preformed mediators.

Question 17

What are the symptoms associated with an allergic acute phase response and why do they occur?

Answer 17

Hypotension - vasodilation
Confusion - reduced cerebral blood flow
GI symptoms - smooth muscle contraction
Tachycardia - reduced resistance and coronary blood flow
Bronchospasm - bronchoconstriction
Angioedema - vascular permeability
Hives/urticarial - histamine and bradykinin

Question 18

Which mast cell mediators are released in the early phase?

Answer 18

Preformed: 
Histamine = vascular permeability
Kallikrein = activates bradykinin for vasodilation
serotonin = smooth muscle contraction
proteases = irritates nerve endings

Question 19

Which mediator can be used to diagnose anaphylaxis and why?

Answer 19

Tryptase as it is the only mediator that lasts 8 hours, all the others are short acting.

Question 20

Which mast cell mediators are released in the late phase and why?

Answer 20

Newly synthesised:
PGs
Cytokines
Leukotrienes
Needed to escalate the response through cell recruitment.

Question 21

What is a biphasic reaction and why does it occur?

Answer 21

Late phase mediators are released 6-8 hours after the initial response is treated, causing an escalated response hours after the initial.

Question 22

How is a biphasic reaction prevented?

Answer 22

Steroids and Antihistamine

Question 23

What is anaphylaxis?

Answer 23

A severe, life-threatening hypersensitivity response, characteristed by a dramatic fall in BP and severe airway constriction (bronchoconstriction or laryngeal oedema). Caused by wide spread vasodilation due to spread of mediators in the circulation.

Question 24

Why is anaphylaxis commonly undiagnosed?

Answer 24

Hives, skin changes and angioedema are not present in 20% of cases and leads to diagnosis of asthma.

Question 25

How is anaphylaxis treated?

Answer 25

Immediate IM adrenaline. Has short half life so can be given every 5 minutes if no improvement seen. 0. 3mg adult and 0.15mg child in community. 0. 5mg adult and 0.01mg per kg child in hospital

Question 26

Why is the dose of adrenaline in the community lower than in a hospital and why is it given IM?

Answer 26

Due to pro-arhythmic action

Question 27

What is a mast cell and its function?

Answer 27

Located in tissues to respond to allergy be releasing histamine. TNFalpha, IL-4 and IL-5 are also released to trigger the cascade.

Question 28

What are basophils?

Answer 28

Circulating mast cells that release histamine, IL-4, IL-13. Can travel to lymph nodes for priming IgE class switching.

Question 29

What are eosinophils and where are they found?

Answer 29

Circulate in blood and migrate into the tissue via chemokines. Production in BM is stimulated by IL-5. Involved in anti-helminth immunity and allergy by releasing mediators from their lysosomal granules.

Question 30

What immune mechanism is involved in anti-helminth immunity?

Answer 30

IgE mediated degranulation upon recognition by mast cells. Helminth are too big for phagocytosis.

Question 31

What is the IgE response to a helminth?

Answer 31

1) Mast cells detect helminth via IgE and release cytokines. 2) IL-5 is released from mast cells to mobilise eosinophils to helminth. 3) Eosinophil attaches to the helminth via FCeR1 region of IgG and IgE . 4) High binding affinity releases contents from lysosomal granules.

Question 32

Which mediators are produced by eosinophils?

Answer 32

MBP (major basic protein) - strong alkali Ribonucleases, peroxidase, proteases ROS and nitrogen radicals

Question 33

Why might tissue damage occur as a result of eosinophil immune response?

Answer 33

Mast cells release eosinophil chemotactic factor causing eosinophils to accumulate and release mediators within tissues causing damage e.g. lung damage in asthma Pts.

Question 34

How is the helminth eradicated after it has been killed by eosinophils?

Answer 34

IL-13 production from eosinophils causes goblet cell hyperplasia and increased mucus production helping to pass helminth through the GIT. Also stimulates contraction of GIT smooth muscle. Also affects lungs so may get bronchoconstriction.